Sex Differences and Hormonal Influences in Human Sensorimotor Gating: Implications for Schizophrenia (original) (raw)
Aasen I, Kolli L, Kumari V (2005) Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies. J Psychopharmacol 19:39–45 ArticlePubMed Google Scholar
Abel K, Waikar M, Pedro B, Hemsley D, Geyer M (1998) Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls. J Psychopharmacol 12:330–337 ArticlePubMedCAS Google Scholar
Anthony BJ (1985) In the blink of an eye: implications of reflex modification for information processing. In: Ackles P et al (eds) Advances in psychophysiology, vol 1. JAI Press, Greenwich, CT, pp 167–218 Google Scholar
Bannbers E, Kask K, Wikstrom J, Sundstrom Poromaa I (2010) Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women. Psychoneuroendocrinology 35:422–429 ArticlePubMedCAS Google Scholar
Barbaccia ML (2004) Neurosteroidogenesis: relevance to neurosteroid actions in brain and modulation by psychotropic drugs. Crit Rev Neurobiol 16:67–74 ArticlePubMedCAS Google Scholar
Barbaccia ML, Affricano D, Purdy RH, Maciocco E, Spiga F, Biggio G (2001) Clozapine, but not haloperidol, increases brain concentrations of neuroactive steroids in the rat. Neuropsychopharmacology 25:489–497 ArticlePubMedCAS Google Scholar
Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology l5(4):339–343 Google Scholar
Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47:181–188 ArticlePubMedCAS Google Scholar
Braff DL, Geyer MA, Swerdlow NR (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl) 156:234–258 ArticleCAS Google Scholar
Breier A, Buchanan RW (1992) The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients. Life Sci 51:1527–1534 ArticlePubMedCAS Google Scholar
Brown JS, Kalish HI, Farber IE (1951) Conditioned fear as revealed by magnitude of startle response to an auditory stimulus. J Exp Psychol 41:317–328 ArticlePubMedCAS Google Scholar
Cadenhead KS, Carasso BS, Swerdlow NR, Geyer MA, Braff DL (1999) Prepulse inhibition and habituation of the startle response are stable neurobiological measures in a normal male population. Biol Psychiatry 45:360–364 ArticlePubMedCAS Google Scholar
Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL (2000) Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 157:1660–1668 ArticlePubMedCAS Google Scholar
Carpenter WT, Koenig JI (2008) The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology 33:2061–2079 ArticlePubMedCASPubMed Central Google Scholar
Castle DJ, Murray RM (1991) The neurodevelopmental basis of sex differences in schizophrenia. Psychol Med 21:565–575 ArticlePubMedCAS Google Scholar
Castle DJ, Abel K, Takei N, Murray RM (1995) Gender differences in schizophrenia: hormonal effect or subtypes? Schizophr Bull 21:1–12 ArticlePubMedCAS Google Scholar
Dawson ME, Schell AM, Swerdlow NR, Filion DL (1997) Cognitive, clinical, and neuropsychological implications of startle modulation. In: Lang P et al (eds) Attention and orienting: sensory and motivational processes. Lawrence Erlbaum Associates, Hillsdale, NJ, pp 257–279 Google Scholar
Dluzen DE, Ramirez VD (1984) Bimodal effect of progesterone on in vitro dopamine function of the rat corpus striatum. Neuroendocrinology 39:149–155 ArticlePubMedCAS Google Scholar
Dluzen DE, Ramirez VD (1990) In vitro progesterone modulates amphetamine-stimulated dopamine release from the corpus striatum of castrated male rats treated with estrogen. Neuroendocrinology 52:517–520 ArticlePubMedCAS Google Scholar
Evans LH, Gray NS, Snowden RJ (2005) Prepulse inhibition of startle and its moderation by schizotypy and smoking. Psychophysiology 42:223–231 ArticlePubMed Google Scholar
Faraday MM, O'Donoghue VA, Grunberg NE (1999) Effects of nicotine and stress on startle amplitude and sensory gating depend on rat strain and sex. Pharmacol Biochem Behav 62:273–284 ArticlePubMedCAS Google Scholar
Faraone SV, Chen WJ, Goldstein JM, Tsuang MT (1994) Gender differences in age at onset of schizophrenia. Br J Psychiatry 164:625–629 ArticlePubMedCAS Google Scholar
Fendt M, Li L, Yeomans JS (2001) Brain stem circuits mediating prepulse inhibition of the startle reflex. Psychopharmacology (Berl) 156:216–224 ArticleCAS Google Scholar
Geyer MA, Swerdlow NR, Mansbach RS, Braff DL (1990) Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 25:485–498 ArticlePubMedCAS Google Scholar
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 156:117–154 ArticleCAS Google Scholar
Gogos A, Van den Buuse M (2004) Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1A receptor agonist 8-hydroxy-2-dipropylaminotetralin. J Pharmacol Exp Ther 309:267–274 ArticlePubMedCAS Google Scholar
Gogos A, Nathan PJ, Guille V, Croft RJ, van den Buuse M (2006) Estrogen prevents 5-HT1A receptor-induced disruptions of prepulse inhibition in healthy women. Neuropsychopharmacology 31:885–889 ArticlePubMedCAS Google Scholar
Gottschalk LA, Haer JL, Bates DE (1972) Effect of sensory overload on psychological state. Changes in social alienation-personal disorganization and cognitive-intellectual impairment. Arch Gen Psychiatry 27:451–457 ArticlePubMedCAS Google Scholar
Graham FK (1975) Presidential Address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology 12:238–248 ArticlePubMedCAS Google Scholar
Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Mintz J, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Schork NJ (2007) Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry 64:1242–1250 ArticlePubMed Google Scholar
Guillin O, Abi-Dargham A, Laruelle M (2007) Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 78:1–39 ArticlePubMedCAS Google Scholar
Hafner H (2003) Gender differences in schizophrenia. Psychoneuroendocrinology 28(Suppl 2):17–54 ArticlePubMed Google Scholar
Hafner H, Maurer K, Loffler W, Riecher-Rossler A (1993) The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiatry 162:80–86 ArticlePubMedCAS Google Scholar
Hafner H, an der Heiden W, Behrens S, Gattaz WF, Hambrecht M, Loffler W, Maurer K, Munk-Jorgensen P, Nowotny B, Riecher-Rossler A, Stein A (1998) Causes and consequences of the gender difference in age at onset of schizophrenia. Schizophr Bull 24:99–113 ArticlePubMedCAS Google Scholar
Hasenkamp W, Epstein MP, Green A, Wilcox L, Boshoven W, Lewison B, Duncan E (2010) Heritability of acoustic startle magnitude, prepulse inhibition, and startle latency in schizophrenia and control families. Psychiatry Res 178:236–243 ArticlePubMedPubMed Central Google Scholar
Hazlett EA, Buchsbaum MS (2001) Sensorimotor gating deficits and hypofrontality in schizophrenia. Front Biosci 6:D1069–D1072 ArticlePubMedCAS Google Scholar
Hazlett EA, Buchsbaum MS, Zhang J, Newmark RE, Glanton CF, Zelmanova Y, Haznedar MM, Chu KW, Nenadic I, Kemether EM, Tang CY, New AS, Siever LJ (2008) Frontal-striatal-thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating. Neuroimage 42:1164–1177 ArticlePubMedPubMed Central Google Scholar
Hoffman HS, Searle JL (1968) Acoustic and temporal factors in the evocation of startle. J Acoust Soc Am 43:269–282 ArticlePubMedCAS Google Scholar
Ison JR, Allen PD (2007) Pre- but not post-menopausal female CBA/CaJ mice show less prepulse inhibition than male mice of the same age. Behav Brain Res 185:76–81 ArticlePubMed Google Scholar
Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajos M (2008) Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev Drug Discov 7:68–83 ArticlePubMedCASPubMed Central Google Scholar
Jovanovic T, Szilagyi S, Chakravorty S, Fiallos AM, Lewison BJ, Parwani A, Schwartz MP, Gonzenbach S, Rotrosen JP, Duncan EJ (2004) Menstrual cycle phase effects on prepulse inhibition of acoustic startle. Psychophysiology 41:401–406 ArticlePubMed Google Scholar
Justice AJ, de Wit H (1999) Acute effects of d-amphetamine during the follicular and luteal phases of the menstrual cycle in women. Psychopharmacology (Berl) 145:67–75 ArticleCAS Google Scholar
Kapur S, Remington G (2001) Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biol Psychiatry 50:873–883 ArticlePubMedCAS Google Scholar
Kask K, Backstrom T, Gulinello M, Sundstrom-Poromaa I (2008) Lower levels of prepulse inhibition of startle response in pregnant women compared to postpartum women. Psychoneuroendocrinology 33:100–107 ArticlePubMed Google Scholar
Khisti RT, Mandhane SN, Chopde CT (1998) The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one induces catalepsy in mice. Neurosci Lett 251:85–88 ArticlePubMedCAS Google Scholar
Khisti RT, Deshpande LS, Chopde CT (2002) The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents. Psychopharmacology (Berl) 161:120–128 ArticleCAS Google Scholar
Koch M (1998) Sensorimotor gating changes across the estrous cycle in female rats. Physiol Behav 64:625–628 ArticlePubMedCAS Google Scholar
Kulkarni J (2009) Oestrogen – a new treatment approach for schizophrenia? Med J Aust 190:S37–S38 PubMed Google Scholar
Kumari V, Antonova E, Geyer MA, Ffytche D, Williams SC, Sharma T (2007a) A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics. Int J Neuropsychopharmacol 10:463–477 ArticlePubMedCAS Google Scholar
Kumari V, Antonova E, Geyer MA (2008b) Prepulse inhibition and "psychosis-proneness" in healthy individuals: an fMRI study. Eur Psychiatry 23:274–280 ArticlePubMed Google Scholar
Kumari V, Aasen I, Papadopoulos A, Bojang F, Poon L, Halari R, Cleare AJ (2008a) A comparison of prepulse inhibition in pre- and postmenopausal women and age-matched men. Neuropsychopharmacology 33:2610–2618 ArticlePubMedCAS Google Scholar
Kumari V, Aasen I, Sharma T (2004) Sex differences in prepulse inhibition deficits in chronic schizophrenia. Schizophr Res 69:219–235 ArticlePubMed Google Scholar
Kumari V, Antonova E, Zachariah E, Galea A, Aasen I, Ettinger U, Mitterschiffthaler MT, Sharma T (2005a) Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans. Neuroimage 26:1052–1058 ArticlePubMed Google Scholar
Kumari V, Das M, Zachariah E, Ettinger U, Sharma T (2005b) Reduced prepulse inhibition in unaffected siblings of schizophrenia patients. Psychophysiology 42(5):588–594 Google Scholar
Kumari V, Fannon D, Sumich AL, Sharma T (2007b) Startle gating in antipsychotic-naive first episode schizophrenia patients: one ear is better than two. Psychiatry Res 151:21–28 ArticlePubMed Google Scholar
Kumari V, Gray J, Gupta P, Luscher S, Sharma T (2003a) Sex differences in prepulse inhibition of the acoustic startle response. Person Indiv Diff 34:733–742 Article Google Scholar
Kumari V, Gray JA, Geyer MA, ffytche D, Soni W, Mitterschiffthaler MT, Vythelingum GN, Simmons A, Williams SC, Sharma T (2003b) Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects. Psychiatry Res 122:99–113 ArticlePubMed Google Scholar
Kumari V, Konstantinou J, Papadopoulos A, Aasen I, Poon L, Halari R, Cleare AJ (2010) Evidence for a role of progesterone in menstrual cycle-related variability in prepulse inhibition in healthy young women. Neuropsychopharmacology 35:929–937 ArticlePubMedCASPubMed Central Google Scholar
Kumari V, Peters ER, Fannon D, Premkumar P, Aasen I, Cooke MA, Anilkumar AP, Kuipers E (2008c) Uncontrollable voices and their relationship to gating deficits in schizophrenia. Schizophr Res 101:185–194 ArticlePubMedPubMed Central Google Scholar
Kumari V, Soni W, Mathew VM, Sharma T (2000) Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication. Arch Gen Psychiatry 57:609–614 ArticlePubMedCAS Google Scholar
Kumari V, Toone B, Gray JA (1997) Habituation and prepulse inhibition of the acoustic startle reflex: Effects of smoking status and psychosis-proneness. Pers Individ Dif 23:183–191 Article Google Scholar
Marshall JC (2001) Hormonal regulation of the menstrual cycle and mechanisms of ovulation. In: Leslie J et al (eds) Endocrinology. W.B. Saunders Company, Phliladelphia, pp 2073–2085 Google Scholar
Marx CE, Duncan GE, Gilmore JH, Lieberman JA, Morrow AL (2000) Olanzapine increases allopregnanolone in the rat cerebral cortex. Biol Psychiatry 47:1000–1004 ArticlePubMedCAS Google Scholar
Marx CE, VanDoren MJ, Duncan GE, Lieberman JA, Morrow AL (2003) Olanzapine and clozapine increase the GABAergic neuroactive steroid allopregnanolone in rodents. Neuropsychopharmacology 28:1–13 ArticlePubMedCAS Google Scholar
Marx CE, Shampine LJ, Duncan GE, VanDoren MJ, Grobin AC, Massing MW, Madison RD, Bradford DW, Butterfield MI, Lieberman JA, Morrow AL (2006) Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy? Pharmacol Biochem Behav 84:598–608 ArticlePubMedCAS Google Scholar
Michanek A, Meyerson BJ (1982) Influence of estrogen and progesterone on behavioral effects of apomorphine and amphetamine. Pharmacol Biochem Behav 16:875–879 ArticlePubMedCAS Google Scholar
Montag C, Hartmann P, Merz M, Burk C, Reuter M (2008) D2 receptor density and prepulse inhibition in humans: negative findings from a molecular genetic approach. Behav Brain Res 187:428–432 ArticlePubMedCAS Google Scholar
Neuner I, Stocker T, Kellermann T, Ermer V, Wegener HP, Eickhoff SB, Schneider F, Shah NJ (2010) Electrophysiology meets fMRI: neural correlates of the startle reflex assessed by simultaneous EMG-fMRI data acquisition. Hum Brain Mapp 31:1675–1685 PubMed Google Scholar
Oades RD, Schepker R (1994) Serum gonadal steroid hormones in young schizophrenic patients. Psychoneuroendocrinology 19:373–385 ArticlePubMedCAS Google Scholar
Ornitz EM, Guthrie D, Sadeghpour M, Sugiyama T (1991) Maturation of prestimulation-induced startle modulation in girls. Psychophysiology 28:11–20 ArticlePubMedCAS Google Scholar
Parducz A, Hoyk Z, Kis Z, Garcia-Segura LM (2002) Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapses. Eur J Neurosci 16:665–670 ArticlePubMedCAS Google Scholar
Petrovsky N, Quednow BB, Ettinger U, Schmechtig A, Mössner R, Collier DA, Kühn KU, Maier W, Wagner M, Kumari V (2010) Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers. Neuropsychopharmacology 35:1429–1439 ArticlePubMedCASPubMed Central Google Scholar
Postma P, Gray JA, Sharma T, Geyer M, Mehrotra R, Das M, Zachariah E, Hines M, Williams SC, Kumari V (2006) A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia. Psychopharmacology (Berl) 184:589–599 ArticleCAS Google Scholar
Quednow BB, Kuhn KU, Mossner R, Schwab SG, Schuhmacher A, Maier W, Wagner M (2008) Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms. Biol Psychiatry 64:434–437 ArticlePubMedCAS Google Scholar
Quednow BB, Schmechtig A, Ettinger U, Petrovsky N, Collier DA, Vollenweider FX, Wagner M, Kumari V (2009) Sensorimotor gating depends on polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase, but not on neuregulin-1 Arg38Gln genotype: a replication study. Biol Psychiatry 66:614–620 ArticlePubMedCASPubMed Central Google Scholar
Ramirez VD, Zheng J (1996) Membrane sex-steroid receptors in the brain. Front Neuroendocrinol 17:402–439 ArticlePubMedCAS Google Scholar
Riecher-Rossler A, Hafner H, Stumbaum M, Maurer K, Schmidt R (1994) Can estradiol modulate schizophrenic symptomatology? Schizophr Bull 20:203–214 ArticlePubMedCAS Google Scholar
Roussos P, Giakoumaki SG, Bitsios P (2008a) The dopamine D(3) receptor Ser9Gly polymorphism modulates prepulse inhibition of the acoustic startle reflex. Biol Psychiatry 64:235–240 ArticlePubMedCAS Google Scholar
Roussos P, Giakoumaki SG, Rogdaki M, Pavlakis S, Frangou S, Bitsios P (2008b) Prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism. Psychol Med 38:1651–1658 ArticlePubMedCAS Google Scholar
Rupprecht R (2003) Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties. Psychoneuroendocrinology 28:139–168 ArticlePubMedCAS Google Scholar
Rupprecht R, Koch M, Montkowski A, Lancel M, Faulhaber J, Harting J, Spanagel R (1999) Assessment of neuroleptic-like properties of progesterone. Psychopharmacology (Berl) 143:29–38 ArticleCAS Google Scholar
Shulman Y, Tibbo PG (2005) Neuroactive steroids in schizophrenia. Can J Psychiatry 50:695–702 PubMed Google Scholar
Swerdlow NR, Auerbach P, Monroe SM, Hartston H, Geyer MA, Braff DL (1993) Men are more inhibited than women by weak prepulses. Biol Psychiatry 34:253–260 ArticlePubMedCAS Google Scholar
Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51:139–154 ArticlePubMedCAS Google Scholar
Swerdlow NR, Hartman PL, Auerbach PP (1997) Changes in sensorimotor inhibition across the menstrual cycle: implications for neuropsychiatric disorders. Biol Psychiatry 41:452–460 ArticlePubMedCAS Google Scholar
Swerdlow NR, Geyer MA, Hartman PL, Sprock J, Auerbach PP, Cadenhead K, Perry W, Braff DL (1999) Sex differences in sensorimotor gating of the human startle reflex: all smoke? Psychopharmacology (Berl) 146:228–232 ArticleCAS Google Scholar
Swerdlow NR, Geyer MA, Braff DL (2001) Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl) 156:194–215 ArticleCAS Google Scholar
Swerdlow NR, Stephany N, Wasserman LC, Talledo J, Shoemaker J, Auerbach PP (2003) Amphetamine effects on prepulse inhibition across-species: replication and parametric extension. Neuropsychopharmacology 28:640–650 ArticlePubMedCAS Google Scholar
Swerdlow NR, Light GA, Cadenhead KS, Sprock J, Hsieh MH, Braff DL (2006a) Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. Arch Gen Psychiatry 63:1325–1335 ArticlePubMed Google Scholar
Swerdlow NR, Talledo J, Sutherland AN, Nagy D, Shoemaker JM (2006b) Antipsychotic effects on prepulse inhibition in normal 'low gating' humans and rats. Neuropsychopharmacology 31:2011–2021 ArticlePubMedCAS Google Scholar
Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (2008) Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology (Berl) 199:331–388 ArticleCASPubMed Central Google Scholar
Taherianfard M, Shariaty M (2004) Evaluation of serum steroid hormones in schizophrenic patients. Indian J Med Sci 58:3–9 PubMedCAS Google Scholar
Takahashi H, Iwase M, Ishii R, Ohi K, Fukumoto M, Azechi M, Ikezawa K, Kurimoto R, Canuet L, Nakahachi T, Iike N, Tagami S, Morihara T, Okochi M, Tanaka T, Kazui H, Yoshida T, Tanimukai H, Yasuda Y, Kudo T, Hashimoto R, Takeda M (2008) Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia. Neurosci Res 62:187–194 ArticlePubMed Google Scholar
Talledo JA, SutherlandOwens AN, Schortinghuis T, Swerdlow NR (2009) Amphetamine effects on startle gating in normal women and female rats. Psychopharmacology (Berl) 204:165–175 ArticleCAS Google Scholar
Vaillancourt C, Cyr M, Rochford J, Boksa P, Di Paolo T (2002) Effects of ovariectomy and estradiol on acoustic startle responses in rats. Pharmacol Biochem Behav 74:103–109 ArticlePubMedCAS Google Scholar
Valera S, Ballivet M, Bertrand D (1992) Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 89:9949–9953 ArticlePubMedCASPubMed Central Google Scholar
Wetzel CH, Hermann B, Behl C, Pestel E, Rammes G, Zieglgansberger W, Holsboer F, Rupprecht R (1998) Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor. Mol Endocrinol 12:1441–1451 ArticlePubMedCAS Google Scholar